Buenos Aires  is the starting point—and the flashpoint—of Argentine history. Time has transformed, if not erased, the colonial quarters of Monserrat  and San Telmo , but it’s the epic of independence, the era of immigration and excess, the populism of the Peróns, and the ruthless 1976–1983 dictatorship that helped create contemporary Argentina.
What is now northwestern Argentina was only an outlier of the fabled Inka empire, but there are plenty of pre-Inka archaeological sites in Jujuy’s Quebrada de Humahuaca, the Salta highlands and other Andean provinces, and Córdoba  and its Sierras. History plays second fiddle to nature in Mesopotamia, at least at Iguazú , but Jesuit mission ruins  tell an epic story in their own right.
Arrive at Aeropuerto Internacional Ministro Pistarini (Ezeiza) and transfer to a Buenos Aires hotel. The afternoon is for visiting historic sites like Plaza de Mayo , the Casa Rosada  presidential palace, and the Congreso Nacional .
Travel overland to the landmark Jesuit mission at San Ignacio  and smaller ruined missions en route, with an overnight at the city of Posadas . From Posadas, time permitting, take an excursion across the Paraguayan border to the well-preserved missions of Trinidad and Jesús .
Fly to Buenos Aires and backtrack to the colonial city of Salta, with the afternoon free to visit the city’s colonial churches, monuments, and museums.
Take in a full-day tour of the altiplano high steppe; in the winter dry season, ride the Train to the Clouds.
After an excursion to the archaeological sites and colonial monuments of the Quebrada de Humahuaca, a World Heritage Site in Jujuy Province, overnight in scenic Purmamarca or Tilcara.
Enjoy a morning tour to the remote and stunningly scenic Andean village of Iruya, returning to Salta in the afternoon.
Head out by rental car for the town of Cafayate via the colorful desert canyon of the Quebrada de Cafayate, with a side trip to the pre-Columbian ruins of Quilmes. Sample Cafayate’s unique white wine, torrontés, at any of several local bodegas.
On the return loop to Salta, stop at the scenic Andean village of Cachi and Parque Nacional Los Cardones.
Travel overland to the pilgrimage center of Luján, Argentina’s single most important religious site, and the gaucho capital of San Antonio de Areco.
Ferry across the River Plate to the World Heritage Site of Colonia, Uruguay.